FORTIFY – Focused Orticumab Research for Treating inflammation in Coronary Arteries

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Abcentra LLC

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Cardiovascular Diseases [C14]

Trial duration

21 Oct 2025 → ongoing

Decision date (initial)

2025-08-19

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Abcentra LLC

External identifiers

EU CT number

2025-520464-17-00

WHO UTN

U1111-1318-8403

ClinicalTrials.gov

NCT06927739

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety, Therapy, Dose response, Pharmacodynamic, Others, Pharmacokinetic

To determine the clinical effect of orticumab treatment on inflammation in study participants with prior myocardial infarction who have elevated coronary inflammation based on pericoronary FAI measured during CCTA

Secondary objectives 4

1. 1. To determine the clinical effects of orticumab treatment on other coronary artery perivascular adipose tissue attenuation parameters measured during CCTA
2. 2. To assess the safety and tolerability of orticumab in study participants
3. 3. To determine anti-drug antibodies (ADA) to orticumab
4. 4. To determine serum concentrations of orticumab

Conditions and MedDRA coding

Atherosclerotic Cardiovascular disease

Study design 3 periods

Regulatory references

Scientific advice from competent authorities

Danish Medicines Agency, European Medicines Agency, Food And Drug Administration

Plan to share IPD

Yes

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. 1. Participant must provide informed consent before any study specific activities are performed, must be able and willing to meet all requirements for randomization and must adhere to the schedules of activities.
2. 2. Participant must be >180 days after presumed type-1 myocardial infarction (i.e., due to plaque rupture or erosion, either STEMI or NSTEMI) without subsequent unstable or severe angina (Canadian Cardiovascular Society Class 3 or 4) at the time of enrollment. Participants who have undergone PCI are allowed.
3. 3. Participant must be on a stable cardiovascular treatment regimen consistent with local treatment guidelines for post-AMI patients (such as maximally tolerated statin and/or PCSK9 inhibitor medication for LDL reduction, antiplatelet medication, and hypertension treatment).
4. 4. Participant must have an evaluable, pre-randomization CCTA with one of the following: • A quantifiable Fat Attenuation Index (FAI) Score greater than or equal to the 50th centile (per reference standard) for their age group in at least two coronary arteries or • A quantifiable Fat Attenuation Index (FAI) Score greater than or equal to the 75th centile (per reference standard) for their age group in at least one coronary artery
5. 5. Participant must have body mass index (BMI) ≤ 40 kg/m2.
6. 6. Adult male and female participants ≥18 years of age at the Screening Visit: For female participants, the participant must not be pregnant or lactating and must be one of the following: a) Postmenopausal b) Documentation of irreversible surgical sterilization by hysterectomy, bilateral oophorectomy, or bilateral salpingectomy. c)Females of childbearing potential must have a negative serum or urine pregnancy test prior to the start of study drug, and agree to use a highly effective method of contraception from Baseline through 100 days after the last dose of study For male participants - Nonsterile male participants with sexual partners of childbearing potential must agree to use an adequate method of contraception such as condom, from Baseline through 100 days after last dose of the study drug.

Exclusion criteria 20

1. 1.      History of any clinically important disease or disorder which, in the opinion of the investigator, may either put the participant at risk because of participation in the study, or influence the results or the participant's ability to participate in the study.
2. 2. Percutaneous coronary intervention or invasive diagnostic coronary angiogram planned after screening. Eligible participants who have an invasive diagnostic coronary angiogram performed in the absence of undergoing a new PCI may continue screening after the diagnostic angiogram has been performed or may be rescreened.
3. 3. History of or planned coronary artery bypass grafting.
4. 4. Documented episode of post-MI pericarditis in the 3 months before enrollment.
5. 5. Presence of unstable or uncontrolled angina. Canadian CV society (CCS) angina class > 2.
6. 6. Ongoing New York Heart Association Class IV HF.
7. 7. Poorly controlled type 1 or type 2 diabetes mellitus (hemoglobin A1c >8.0%).
8. 8. Increased risk of bleeding
9. 9. History or presence of any of the following: a) Ongoing infection or febrile illness. b) Ongoing persistent or permanent atrial fibrillation or flutter. c) Cancer within 5 years before randomization, with the exception of non-melanoma skin cancer. d) Alcohol or substance abuse within 6 months before randomization, as judged by the investigator. e) Known history of hypersensitivity reactions to other biologics, to human IgG preparations, or to any component of orticumab, or ongoing severe allergy as judged by the investigator. f) Active positive results on screening for serum hepatitis C core antibody. g) Clinically documented hepatitis B or HIV.
10. 10. Any clinically important abnormalities in clinical chemistry, hematology, coagulation parameters, as judged by the investigator
11. 11. Blood pressure values at screening (taken as the average of triplicate measurements): a) Systolic blood pressure < 90 mmHg or > 180 mmHg. b) Diastolic blood pressure > 100 mmHg. c) One triplicate retest (repeat of all 3) will be allowed during the same visit, at which point if the retest result is no longer exclusionary, the participant may be randomized d) Participants who are excluded based on elevated blood pressure may be rescreened following adequate treatment.
12. 12. Participants with contraindications to CCTA
13. 13. Use of any of the following in the 180 days before randomization: IL-17 inhibitor, TNF inhibitor, IL-6 inhibitor, IL-1β inhibitor, methotrexate, cyclosporine, apremilast, colchicine, systemic steroids (topical steroid and inhaled steroid use is allowed).
14. 14. COVID-19 vaccine within 90 days of screening CCTA.
15. 15. Participants with a confirmed positive COVID-19 test within 90 days of screening CCTA.
16. 16. Receipt of any investigational device or therapy within 6 months or 5 half-lives before screening (whichever is longer).
17. 17. Planned participation in an additional investigational study of an intervention or biologic before the end of the follow-up period. Participation in observational studies or studies without investigational drugs or devices is allowed.
18. 18. Participants who have previously been exposed to orticumab.
19. 19. Participants who are legally institutionalized.
20. 20. An employee or close relative of an employee of the sponsor, the CRO, or the study site, regardless of the employee or close relative's role.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Percent change from baseline of the mean Fat Attenuation Index (FAI) score for the 3 coronary arteries (RCA, LAD, LCX), calculated as the average of the analyzable FAI scores (valid baseline and post-baseline FAI score) across the three main coronary arteries, for orticumab compared to placebo after 6 months of treatment

Secondary endpoints 9

1. 1. Change from baseline for FAI, FAI score (mean absolute change and mean percent change) and FAI score centile for orticumab compared to placebo after 6 months of treatment in the following vessels: o Greatest change in most inflamed vessel o Greatest change in any vessel o RCA only analysis o LAD only analysis o LCX only analysis
2. 2. Mean absolute change from baseline for mean FAI and mean FAI score, defined as the average of the analyzable vessels (with valid baseline FAI and post-baseline FAI) across the three main coronary arteries (RCA, LAD, LCX)
3. 3. Change from baseline for CaRi-Heart risk score (mean absolute change and mean percent change) for orticumab compared to placebo after 6 months of treatment
4. 4. Number and percent of participants with treatment-emergent adverse events (TEAEs), and any serious adverse events
5. 5. Change from baseline in systolic blood pressure, diastolic blood pressure and pulse rate measurements
6. 6. Change from baseline in clinical safety laboratory parameters
7. 7. Change from baseline in physical examinations
8. 8. Serum ADA titers measured at baseline and at specified times over the 6-month treatment period
9. 9. Serum trough orticumab concentrations following an orticumab dose

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Abcentra LLC

Sponsor organisation

Abcentra LLC

Address

1925 Century Park East Suite 1700

City

Los Angeles

Postcode

90067-2740

Country

United States

Scientific contact point

Organisation

Abcentra LLC

Contact name

FORTIFY Study Team

Public contact point

Organisation

Abcentra LLC

Contact name

FORTIFY Study Team

Third parties 6

Locations

7 EU/EEA countries · 30 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 58 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

5 submissions — initial application plus substantial / non-substantial modifications